Molecular imaging of a fluorescent antibody against epidermal growth factor receptor detects high-grade glioma.
Molecular imaging of a fluorescent antibody against epidermal growth factor receptor detects high-grade glioma.
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DOI：
10.1038/s41598-021-84831-4
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发表时间：
2021-03-11
影响因子：
4.6
通讯作者：
Grant GA
中科院分区：
文献类型：
--
作者：
Zhou Q;Vega Leonel JCM;Santoso MR;Wilson C;van den Berg NS;Chan CT;Aryal M;Vogel H;Cayrol R;Mandella MJ;Schonig F;Lu G;Gambhir SS;Moseley ME;Rosenthal EL;Grant GA
高级别胶质瘤（HGG）的预后仍然令人沮丧，切除的程度与总生存期和无进展疾病相关。表皮生长因子受体（EGFR）是HGG中异质表达的生物标志物。我们评估了利用靶向EGFR的近红外荧光抗体检测HGG的可行性。在全身注射panitumumab-IRDye800后，对EGFR表达适度的原位HGG异种移植物小鼠进行体内成像，以评估其在14天内的宏观和体外显微镜下的肿瘤特异性摄取。病理学家对35例HGG患者59例肿瘤标本的EGFR免疫组化染色进行评分，并与小鼠异种移植物的表达水平进行比较。panitumumab-IRDye800的肿瘤内分布与近红外荧光和EGFR表达相关。荧光鉴别肿瘤细胞的特异性为90%，敏感性为82.5%。panitumumab-IRDye800输注后14小时，靶本比达到峰值，分别达到体内19.5和离体7.6。77.1%的HGG患者的EGFR蛋白表达与小鼠异种移植物相当或更高。年龄，结合idh野生型脑肿瘤，可以预测人类肿瘤中更高的EGFR蛋白表达。尽管EGFR表达适度，但肿瘤特异性摄取panitumumab-IRDye800提供了显著的对比和灵活的荧光引导鉴定HGGs的成像窗口。
The prognosis for high-grade glioma (HGG) remains dismal and the extent of resection correlates with overall survival and progression free disease. Epidermal growth factor receptor (EGFR) is a biomarker heterogeneously expressed in HGG. We assessed the feasibility of detecting HGG using near-infrared fluorescent antibody targeting EGFR. Mice bearing orthotopic HGG xenografts with modest EGFR expression were imaged in vivo after systemic panitumumab-IRDye800 injection to assess its tumor-specific uptake macroscopically over 14 days, and microscopically ex vivo. EGFR immunohistochemical staining of 59 tumor specimens from 35 HGG patients was scored by pathologists and expression levels were compared to that of mouse xenografts. Intratumoral distribution of panitumumab-IRDye800 correlated with near-infrared fluorescence and EGFR expression. Fluorescence distinguished tumor cells with 90% specificity and 82.5% sensitivity. Target-to-background ratios peaked at 14 h post panitumumab-IRDye800 infusion, reaching 19.5 in vivo and 7.6 ex vivo, respectively. Equivalent or higher EGFR protein expression compared to the mouse xenografts was present in 77.1% HGG patients. Age, combined with IDH-wildtype cerebral tumor, was predictive of greater EGFR protein expression in human tumors. Tumor specific uptake of panitumumab-IRDye800 provided remarkable contrast and a flexible imaging window for fluorescence-guided identification of HGGs despite modest EGFR expression.
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影响因子：
4.1
作者：
Lau, Darryl;Hervey-Jumper, Shawn L.;Berger, Mitchel S.
通讯作者：
Berger, Mitchel S.
影响因子：
3.7
作者：
Hatakeyama H;Cheng H;Wirth P;Counsell A;Marcrom SR;Wood CB;Pohlmann PR;Gilbert J;Murphy B;Yarbrough WG;Wheeler DL;Harari PM;Guo Y;Shyr Y;Slebos RJ;Chung CH
通讯作者：
Chung CH
影响因子：
1.8
作者：
Belykh E;Martirosyan NL;Yagmurlu K;Miller EJ;Eschbacher JM;Izadyyazdanabadi M;Bardonova LA;Byvaltsev VA;Nakaji P;Preul MC
通讯作者：
Preul MC
影响因子：
3.9
作者：
Miller, Sarah E.;Tummers, Willemieke S.;Rosenthal, Eben L.
通讯作者：
Rosenthal, Eben L.
影响因子：
16.6
作者：
Nishio, Naoki;van den Berg, Nynke S.;Rosenthal, Eben L.
通讯作者：
Rosenthal, Eben L.